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N-ACetylcysteine to Reduce Infection and Mortality for Alcoholic Hepatitis (NACAH)

Primary Purpose

Alcoholic Hepatitis, Infection

Status
Recruiting
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
N-acetyl cysteine (NAC)
Sponsored by
Imperial College London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcoholic Hepatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Aged 18 years or older

  • Clinical alcoholic hepatitis:

    • Serum bilirubin >80umol/L
    • History of alcohol excess (>80g/day male, >60g/day female)
    • Less than 4 weeks since admission to hospital
    • Maddrey's discriminant function (DF) >32
    • Informed consent

Exclusion Criteria:

  • Alcohol abstinence of >6 weeks prior to randomisation
  • Duration of jaundice >3 months

  • Other causes of liver disease including:

    • Evidence of viral hepatitis (hepatitis B or C)
    • Biliary obstruction
    • Hepatocellular carcinoma
  • Evidence of current malignancy (except non-melanotic skin cancer)
  • Previous entry into the study
  • Patients with known hypersensitivity or previous reactions to NAC
  • Pregnant or lactating women

Sites / Locations

  • St Mary's Hospital, Imperial CollegeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

prednisolone+NAC

prednisolone

Arm Description

40mg prednisolone once a day for 28 days and 30 minutes of intravenous NAC at 150mg/kg in 250ml 5% dextrose solution followed by 4 hours of intravenous NAC at 50mg/kg in 500ml 5% dextrose solution, followed by 16 hours of intravenous NAC at 100 mg/kg in 1000ml 5% dextrose solution, followed by 4 days of intravenous NAC at 100mg/kg/day in 1000ml 5% dextrose solution

40mg prednisolone for 28 days

Outcomes

Primary Outcome Measures

Improvement in monocyte oxidative burst
Improvement in ex vivo monocyte oxidative burst

Secondary Outcome Measures

Proportion of patients infected
Infection will be defined in two ways: i. by new/change in intravenous antibiotic prescription and ii. published clinical and microbiological criteria for infection in the setting of liver disease
Proportion of patients infected
Infection will be defined in two ways: i. by new/change in intravenous antibiotic prescription and ii. published clinical and microbiological criteria for infection in the setting of liver disease
Death
Death

Full Information

First Posted
February 28, 2017
Last Updated
November 8, 2021
Sponsor
Imperial College London
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1. Study Identification

Unique Protocol Identification Number
NCT03069300
Brief Title
N-ACetylcysteine to Reduce Infection and Mortality for Alcoholic Hepatitis
Acronym
NACAH
Official Title
The Mechanism of Action of N-acetylcysteine for Reducing the Risk of Infection in Alcoholic Hepatitis
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2015 (Actual)
Primary Completion Date
April 1, 2022 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Recent data have suggested that monocyte oxidative burst defect is associated with the development of infection in patients with severe alcoholic hepatitis. One report found reduced 28 day mortality in patients treated with N-acetylcysteine combined with prednisolone when compared to prednisolone alone. The current study seeks to reveal whether the mechanism by which NAC reduces susceptibility to infection is through improvement of phagocyte oxidative burst.
Detailed Description
Randomised controlled trial, open label.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Hepatitis, Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
randomized controlled trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
prednisolone+NAC
Arm Type
Experimental
Arm Description
40mg prednisolone once a day for 28 days and 30 minutes of intravenous NAC at 150mg/kg in 250ml 5% dextrose solution followed by 4 hours of intravenous NAC at 50mg/kg in 500ml 5% dextrose solution, followed by 16 hours of intravenous NAC at 100 mg/kg in 1000ml 5% dextrose solution, followed by 4 days of intravenous NAC at 100mg/kg/day in 1000ml 5% dextrose solution
Arm Title
prednisolone
Arm Type
No Intervention
Arm Description
40mg prednisolone for 28 days
Intervention Type
Drug
Intervention Name(s)
N-acetyl cysteine (NAC)
Other Intervention Name(s)
NAC
Primary Outcome Measure Information:
Title
Improvement in monocyte oxidative burst
Time Frame
24 hours
Title
Improvement in ex vivo monocyte oxidative burst
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Proportion of patients infected
Description
Infection will be defined in two ways: i. by new/change in intravenous antibiotic prescription and ii. published clinical and microbiological criteria for infection in the setting of liver disease
Time Frame
28 days
Title
Proportion of patients infected
Description
Infection will be defined in two ways: i. by new/change in intravenous antibiotic prescription and ii. published clinical and microbiological criteria for infection in the setting of liver disease
Time Frame
90 days
Title
Death
Time Frame
28 days
Title
Death
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged 18 years or older Clinical alcoholic hepatitis: Serum bilirubin >80umol/L History of alcohol excess (>80g/day male, >60g/day female) Less than 4 weeks since admission to hospital Maddrey's discriminant function (DF) >32 Informed consent Exclusion Criteria: Alcohol abstinence of >6 weeks prior to randomisation Duration of jaundice >3 months Other causes of liver disease including: Evidence of viral hepatitis (hepatitis B or C) Biliary obstruction Hepatocellular carcinoma Evidence of current malignancy (except non-melanotic skin cancer) Previous entry into the study Patients with known hypersensitivity or previous reactions to NAC Pregnant or lactating women
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nikhil Vergis, PhD
Email
nvergis@ic.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Mark Thursz, MD
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Thursz, MD
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Mary's Hospital, Imperial College
City
London
ZIP/Postal Code
W2 1NY
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nikhil Vergis, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
contact investigators
Citations:
PubMed Identifier
22070475
Citation
Nguyen-Khac E, Thevenot T, Piquet MA, Benferhat S, Goria O, Chatelain D, Tramier B, Dewaele F, Ghrib S, Rudler M, Carbonell N, Tossou H, Bental A, Bernard-Chabert B, Dupas JL; AAH-NAC Study Group. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med. 2011 Nov 10;365(19):1781-9. doi: 10.1056/NEJMoa1101214.
Results Reference
background
PubMed Identifier
26860769
Citation
Vergis N, Khamri W, Beale K, Sadiq F, Aletrari MO, Moore C, Atkinson SR, Bernsmeier C, Possamai LA, Petts G, Ryan JM, Abeles RD, James S, Foxton M, Hogan B, Foster GR, O'Brien AJ, Ma Y, Shawcross DL, Wendon JA, Antoniades CG, Thursz MR. Defective monocyte oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NADPH oxidase. Gut. 2017 Mar;66(3):519-529. doi: 10.1136/gutjnl-2015-310378. Epub 2016 Feb 9.
Results Reference
result

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N-ACetylcysteine to Reduce Infection and Mortality for Alcoholic Hepatitis

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